Thursday, April 14, 2016

A multi-institutional study led by a Massachusetts General Hospital (MGH) investigator finds significant racial disparities in the risk that patients being treated for gout will develop a serious, sometimes life-threatening adverse reaction to the most commonly prescribed medication

The increased risk closely correlates with the frequency of a gene variant previously associated with that adverse reaction, supporting recommendations to screen for that variant in patients from those populations. "We found that Asian and black patients have a substantially higher risk of severe cutaneous adverse reactions to urate-lowering drugs than do white or Hispanic patients, which correlates with the frequency of the HLA-B*5801 gene in their U.S. populations," says Hyon K. Choi, MD, DrPH, of the MGH Division of Rheumatology, Allergy and Immunology, senior author of the report. "This risk is almost certainly due to allopurinol, the dominant urate-lowering drug in the U.S., and screening gout patients from those populations for the HLA-B*5801 variant could help increase treatment safety." Caused by excessive levels of uric acid in the body, gout involves the deposition of uric acid crystals in the joints, leading to inflammation and significant pain. Studies have associated the HLA-B*5801 variant with the risk of these reactions in particular Asian populations - Koreans, Japanese, Thai and Han Chinese - and in some Europeans; and the current study was designed to investigate whether the frequency of the HLA-B*5801 variant across races leads to significant racial disparities in the risk of severe cutaneous reactions to urate-lowering drugs in a representative U.S. population. The researchers examined data covering 2009 to 2013 from the Nationwide Inpatient Sample of the Agency for Healthcare Research and Quality. From that database of between 5 and 8 million hospitalizations each year, they identified 606 with a principal diagnosis of SJS/TEN related to an adverse reaction to urate-lowering drugs. While the database does not include information on specific medications, the frequency with which allopurinol is prescribed implies that most, if not all, of those reactions involved that drug, the authors note. Among patients with that diagnosis, there was a significant over-representation of Asian and black patients compared with whites. For example, while another database indicates that Asian patients represented only 2% of U.S. allopurinol users in 2011-12, they represented 27% of those hospitalized for SJS/TEN related to urate-lowering drugs. Black patients represented 13% of allopurinol users and 26% of hospitalizations, while white patients represented 81% of allopurinol users but only 29% of hospitalizations. The number of Hispanic patients in the hospitalization database with this diagnosis was extremely small. Overall the risk of these dangerous reactions was 12 times higher for Asian patients and 5 times higher for black patients compared with white patients. Those differences are closely aligned with the frequency of the HLA-B*5801 variant in those populations - a 7.4% frequency in Asians, 4% in blacks, and 1% in both whites and Hispanics. "Since no other urate-lowering drug is an established cause for these severe adverse reactions, our findings support the use of vigilance when considering allopurinol for Asian and black patients with gout," says Choi, who is a professor of Medicine at Harvard Medical School.

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